Thymopoietin is a polypeptide produced by cells of the thymus and other cells, which has been implicated in various immune and nervous system pathways. There have been several attempts to isolate and sequence various species of thymopoietin. Thymopoietin was originally isolated as a 5 kDa, 49 amino acid protein from bovine thymus [Goldstein et al, Nature, 247:11-14 (1974). See also, Schlesinger and Goldstein, Cell, 5:361-365 (1975).] Later work described by T. Audhya et al, Biochemistry, 20(21):6195-6200 (1981) purported to provide the complete sequences for bovine thymopoietins. Three 49 amino acid sequences were described therein. Zevin-Sonkin et al, Immunol. Lett., 31:301-310 (1992) report the isolation of a bovine cDNA using oligonucleotide probes based on the original 49 amino acid bovine TP protein sequence [Schlesinger and Goldstein, cited above], which encodes the originally determined sequence at the N-terminus of a larger open reading frame.
The active site of thymopoietin, a pentapeptide of the sequence Arg-Lys-Asp-Val-Tyr [SEQ ID NO:7], was described by G. Goldstein et al, Science, 204:1309-1310 (1979) and in U.S. Pat. No. 4,190,646. There is a wealth of art describing analogs of the active site, termed thymopentin and their uses.
Attempts to isolate and sequence thymopoietin continue. For example, European Patent Application 502,607 describes bovine thymopoietin or thymopoietin-like cDNA clones.
Despite these publications and the knowledge of thymopoietin, to date, the cloning of the complete human thymopoietin gene and its recombinant expression has not been described. There remains a need in the art for a convenient method of producing human thymopoietin, fragments thereof, and polynucleotide sequences encoding the protein.